2023
Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children
Kim J, Shimizu C, He M, Wang H, Hoffman H, Tremoulet A, Shyy J, Burns J. Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children. International Journal Of Molecular Sciences 2023, 24: 12318. PMID: 37569694, PMCID: PMC10418493, DOI: 10.3390/ijms241512318.Peer-Reviewed Original ResearchMeSH KeywordsChildConnective Tissue DiseasesCOVID-19Endothelial CellsHumansMucocutaneous Lymph Node SyndromeSystemic Inflammatory Response SyndromeConceptsKawasaki diseaseEndothelial cellsCardiovascular outcomesInflammatory syndromeWeighted gene co-expression network analysisDifferent cardiovascular outcomesMultisystem inflammatory syndromePre-treatment serumEC homeostasisEndothelial-mesenchymal transitionCultured endothelial cellsPro-survival genesClinical manifestationsHealthy controlsImmune responseNFκB pathwayCell responsesEndothelial cell responsesDiseaseGene co-expression network analysisEC responseExpression levelsSyndromeCo-expression network analysisReduced transcripts
2022
RNA Sequencing Reveals Beneficial Effects of Atorvastatin on Endothelial Cells in Acute Kawasaki Disease
Shimizu C, Kim J, He M, Tremoulet A, Hoffman H, Shyy J, Burns J. RNA Sequencing Reveals Beneficial Effects of Atorvastatin on Endothelial Cells in Acute Kawasaki Disease. Journal Of The American Heart Association 2022, 11: e025408. PMID: 35861833, PMCID: PMC9707837, DOI: 10.1161/jaha.122.025408.Peer-Reviewed Original ResearchMeSH KeywordsAtorvastatinEndothelial CellsHuman Umbilical Vein Endothelial CellsHumansImmunoglobulins, IntravenousInflammationInfliximabMucocutaneous Lymph Node SyndromeSequence Analysis, RNAConceptsKawasaki diseaseGenome-wide transcriptional changesIntravenous immunoglobulinAcute Kawasaki diseaseHuman umbilical vein ECsInflammatory cell infiltrationEndothelial cell dysfunctionTumor necrosis factorTranscriptional changesRNA sequencingKD treatmentAcute phaseMyointimal proliferationCoronary arteryCell infiltrationCultured ECsNecrosis factorCell dysfunctionKD seraInterleukin-1Recruitment pathwayResponse of ECBackground damageSerumPatientsAn Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease
Ghosh P, Katkar G, Shimizu C, Kim J, Khandelwal S, Tremoulet A, Kanegaye J, Bocchini J, Das S, Burns J, Sahoo D. An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease. Nature Communications 2022, 13: 2687. PMID: 35577777, PMCID: PMC9110726, DOI: 10.1038/s41467-022-30357-w.Peer-Reviewed Original ResearchMeSH KeywordsArtificial IntelligenceChildComputational BiologyCOVID-19CytokinesGene Expression ProfilingHumansImmunityMucocutaneous Lymph Node SyndromePandemicsSARS-CoV-2Systemic Inflammatory Response SyndromeConceptsKawasaki diseaseHost immune responseLaboratory parametersImmune responseSARS-CoV-2 infectionInflammatory syndromeCytokine stormSerum cytokinesClinical featuresCytokine pathwaysCardiac phenotypeSyndromeGene signaturePediatric syndromesViral pandemicHeart tissueCOVID-19COVID-19 pandemicProximal pathwayDiseaseSeverityImmunopathogenesisPandemicCytokinesIllness
2021
Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles
Jackson H, Menikou S, Hamilton S, McArdle A, Shimizu C, Galassini R, Huang H, Kim J, Tremoulet A, Thorne A, Fischer R, de Jonge M, Kuijpers T, Wright V, Burns J, Casals-Pascual C, Herberg J, Levin M, Kaforou M, On Behalf Of The Perform Consortium. Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles. International Journal Of Molecular Sciences 2021, 22: 5655. PMID: 34073389, PMCID: PMC8198135, DOI: 10.3390/ijms22115655.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentBacterial InfectionsChildChild, PreschoolComputational BiologyFemaleGene Expression ProfilingHumansMaleMucocutaneous Lymph Node SyndromeProteomicsVirus DiseasesConceptsKawasaki diseaseViral infectionHost responseKD patientsAcute inflammatory disordersAnti-bacterial responsePathway analysisBacterial patientsInflammatory disordersInflammatory responsePatient stratificationCommon triggerPatientsKD samplesHost transcriptomicsInfectionProteomic profilesOmics profilesDifferent triggersDiagnostic signatureResponseInflammationTriggersLevelsEtiologyIdentification of novel locus associated with coronary artery aneurysms and validation of loci for susceptibility to Kawasaki disease
Hoggart C, Shimizu C, Galassini R, Wright V, Shailes H, Bellos E, Herberg J, Pollard A, O’Connor D, Choi S, Seaby E, Menikou S, Hibberd M, Sallah N, Burgner D, Brogan P, Patel H, Kim J, Tremoulet A, Salo E, van Stijn D, Kuijpers T, Burns J, Levin M. Identification of novel locus associated with coronary artery aneurysms and validation of loci for susceptibility to Kawasaki disease. European Journal Of Human Genetics 2021, 29: 1734-1744. PMID: 33772158, PMCID: PMC7994355, DOI: 10.1038/s41431-021-00838-5.Peer-Reviewed Original ResearchMeSH KeywordsCaspase 3Coronary AneurysmHumansMucocutaneous Lymph Node SyndromePhosphotransferases (Alcohol Group Acceptor)Polymorphism, Single NucleotideProteinsQuantitative Trait LociReceptors, IgGConceptsGenome-wide association studiesIntergenic regionNovel lociChromosome 20q13Second genome-wide association studyEuropean genome-wide association studyValidation of lociJapanese genome-wide association studiesGWAS summary dataAssociated lociGenomic regionsGenome dataPutative lociDifferent genesRisk allelesAssociation studiesEuropean descentLociGenetic variantsAllelesSNVsWider significanceGenesSusceptibilityCASP3
2019
HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease
Shimizu C, Kim J, Eleftherohorinou H, Wright V, Hoang L, Tremoulet A, Franco A, Hibberd M, Takahashi A, Kubo M, Ito K, Tanaka T, Onouchi Y, Coin L, Levin M, Burns J, Shike H, Consortium O. HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease. Human Immunology 2019, 80: 731-738. PMID: 31122742, PMCID: PMC10793643, DOI: 10.1016/j.humimm.2019.04.020.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAmino Acid SequenceAmino Acid SubstitutionAntigen PresentationBinding SitesCohort StudiesGene FrequencyGenetic Predisposition to DiseaseGenotypeHistocompatibility TestingHLA-C AntigensHumansJapanMucocutaneous Lymph Node SyndromePeptidesPolymorphism, Single NucleotideProtein BindingProtein DomainsT-Lymphocytes, CytotoxicConceptsKawasaki diseaseCytotoxic T cellsSusceptible childrenJapanese cohortRisk A-alleleSingle cohort studyHLA class ISingle nucleotide variantsHLA-C variantsHLA-B geneCohort studyPediatric vasculitisAmino acid substitutionsT cellsKD susceptibilityHLAUnknown triggerA alleleRisk allelesClass ICohortInfluence susceptibilityAcid substitutionsNon-conservative amino acid substitutionsVasculitis
2018
Clustering and climate associations of Kawasaki Disease in San Diego County suggest environmental triggers
Rypdal M, Rypdal V, Burney J, Cayan D, Bainto E, Skochko S, Tremoulet A, Creamean J, Shimizu C, Kim J, Burns J. Clustering and climate associations of Kawasaki Disease in San Diego County suggest environmental triggers. Scientific Reports 2018, 8: 16140. PMID: 30420674, PMCID: PMC6232126, DOI: 10.1038/s41598-018-33124-4.Peer-Reviewed Original ResearchMeSH KeywordsCaliforniaClimateCluster AnalysisEnvironmental MonitoringHumansIncidenceMonte Carlo MethodMucocutaneous Lymph Node SyndromeProspective StudiesTemperatureWeatherConceptsKawasaki diseaseKD casesCases of KDEnvironmental triggersMore environmental triggersCertain clinical characteristicsRegional children's hospitalClinical characteristicsKD patientsChildren's HospitalDisease characteristicsSusceptible childrenHeart diseaseCommon causeDiseaseEpisodic exposurePatientsHospitalGene expression analysisSan Diego CountyGene expression patternsExpression patternsDisease incidenceTemporal clustersBifid T waves on the ECG and genetic variation in calcium channel voltage‐dependent beta 2 subunit gene (CACNB2) in acute Kawasaki disease
Oyamada J, Shimizu C, Kim J, Williams M, Png E, Hibberd M, Tremoulet A, Perry J, Burns J. Bifid T waves on the ECG and genetic variation in calcium channel voltage‐dependent beta 2 subunit gene (CACNB2) in acute Kawasaki disease. Congenital Heart Disease 2018, 14: 213-220. PMID: 30395415, DOI: 10.1111/chd.12696.Peer-Reviewed Original ResearchConceptsBifid T wavesKawasaki diseaseT-wave morphologyKD subjectsT waveIndependent cohortKD susceptibilityAcute KD subjectsAcute Kawasaki diseaseSelf-limited vasculitisSubunit geneGenetic variantsGenotype/phenotype association studiesWide association study dataGenome-wide association study dataIntracellular calcium signalingPhenotype association studiesWave morphologyAssociation study dataCalcium channel geneCommon causeCardiac repolarizationMyocardial repolarizationCardiac diseaseAbnormal repolarization
2017
Whole genome sequencing of an African American family highlights toll like receptor 6 variants in Kawasaki disease susceptibility
Kim J, Shimizu C, Kingsmore S, Veeraraghavan N, Levy E, dos Santos A, Yang H, Flatley J, Hoang L, Hibberd M, Tremoulet A, Harismendy O, Ohno-Machado L, Burns J. Whole genome sequencing of an African American family highlights toll like receptor 6 variants in Kawasaki disease susceptibility. PLOS ONE 2017, 12: e0170977. PMID: 28151979, PMCID: PMC5289527, DOI: 10.1371/journal.pone.0170977.Peer-Reviewed Original ResearchConceptsWhole genome sequencesGenome-wide association studiesToll-like receptor 6Single nucleotide variantsCommon disease-rare variant hypothesisExpression quantitative trait loci (eQTL) analysisDifferential expressionQuantitative trait locus (QTL) analysisCommon disease–common variantPathogen-associated molecular pattern recognitionIntegrative genomics approachIntronic single nucleotide variantsComplex genetic diseasesSequence quality scoresMolecular pattern recognitionWhole-genome sequencingGenomic approachesTranscriptome dataGenome sequenceSequence variationLocus analysisGenome sequencingAssociation studiesFunction of genotypeNucleotide variants
2016
PRINCESS: Privacy-protecting Rare disease International Network Collaboration via Encryption through Software guard extensionS
Chen F, Wang S, Jiang X, Ding S, Lu Y, Kim J, Sahinalp S, Shimizu C, Burns J, Wright V, Png E, Hibberd M, Lloyd D, Yang H, Telenti A, Bloss C, Fox D, Lauter K, Ohno-Machado L. PRINCESS: Privacy-protecting Rare disease International Network Collaboration via Encryption through Software guard extensionS. Bioinformatics 2016, 33: 871-878. PMID: 28065902, PMCID: PMC5860394, DOI: 10.1093/bioinformatics/btw758.Peer-Reviewed Original ResearchMeSH KeywordsComputer SecurityGenetic Association StudiesGenomicsHumansMucocutaneous Lymph Node SyndromePrivacyRare DiseasesSoftwareConceptsSoftware Guard ExtensionsHomomorphic encryptionDistributed ComputationCollaboration frameworkTrustworthy computationCollaboration modelSupplementary dataNetwork collaborationEncryptionExperimental resultsHealth informationAlternative solutionComputationInternational collaboration frameworkHardwareAccurate analysisPerformanceBioinformaticsImplementationFrameworkDataExtensionInformationCollaboration
2013
Differential Expression of miR-145 in Children with Kawasaki Disease
Shimizu C, Kim J, Stepanowsky P, Trinh C, Lau H, Akers J, Chen C, Kanegaye J, Tremoulet A, Ohno-Machado L, Burns J. Differential Expression of miR-145 in Children with Kawasaki Disease. PLOS ONE 2013, 8: e58159. PMID: 23483985, PMCID: PMC3590129, DOI: 10.1371/journal.pone.0058159.Peer-Reviewed Original ResearchMeSH KeywordsArteriesBase SequenceChildChild, PreschoolCluster AnalysisGene Expression RegulationHumansInfantMicroRNAsModels, BiologicalMolecular Sequence DataMucocutaneous Lymph Node SyndromeReal-Time Polymerase Chain ReactionSequence AlignmentSequence Analysis, DNASignal TransductionTransforming Growth Factor betaConceptsTGF-β pathwayGene expressionMiR-145Small non-coding RNAsKawasaki disease pathogenesisExtracellular vesiclesSmall RNA speciesPost-transcriptional levelDiscovery of microRNAsKawasaki diseaseNon-coding RNAsExpression of genesDisease pathogenesisSmall extracellular vesiclesSmall RNAsRNA speciesTarget genesTop pathwaysVascular smooth muscle cellsPathway analysisDifferentiation of neutrophilsDifferential expressionMicroRNAsArterial wallGeneration of myofibroblasts